Aaron M. Kipp

Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting

Objective:To compare incidence and distribution of non-AIDS-defining events (NADEs) among HIV-1-infected adults receiving combination antiretroviral therapy (cART) in urban sub-Saharan African versus United States settings. Design:Retrospective cohort analysis of clinical trial and observational data. Methods:Compared crude and standardized (to US cohort by age and sex) NADE rates from two urban adult HIV-infected cART-initiating populations: a clinical trial cohort in Gaborone, Botswana (Botswana) and an observational cohort in Nashville, Tennessee (USA). Results:Crude NADE incidence rates were similar: 10.0 [95% confidence interval 6.3–15.9] per 1000 person-years in Botswana versus 12.4 [8.4–18.4] per 1000 person-years in the United States. However, after standardizing to an older, predominantly male US population, the overall NADE incidence rates were higher in Botswana [18.7 (8.3–33.1) per 1000 person-years]. Standardized rates differed most for cardiovascular events (8.4 versus 5.0 per 1000 person-years) and non-AIDS-defining malignancies (8.0 versus 0.5 per 1000 person-years) – both higher in Botswana. Conversely, hepatic NADE rates were higher in the United States (4.0 versus 0.0 per 1000 person-years), whereas renal NADE rates [3.0 per 1000 person-years (United States) versus 2.4 per 1000 person-years (Botswana)] were comparable. Conclusion:Crude NADE incidence rates were similar between cART-treated patients in a US observational cohort and a sub-Saharan African clinical trial. However, when standardized to the US cohort, overall NADE rates were higher in Botswana. NADEs appear to be a significant problem in our sub-Saharan African setting, and the monitoring, prevention, and treatment of NADEs should be a critical component of care in resource-limited settings.

Extrapulmonary tuberculosis, human immunodeficiency virus, and foreign birth in North Carolina, 1993 – 2006

BackgroundThe proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important.MethodsCase-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB.ResultsAmong all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23).ConclusionForeign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB.

Relationship between HIV stigma and self-isolation among people living with HIV in Tennessee.

Introduction HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood. Methods Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior. Results Three main themes emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and misperceptions about transmission; (2) acts of discrimination by families, friends, health care providers, and within the workplace; and (3) participants’ use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person’s HIV status made identifying enacted stigma with a quantitative scale difficult. Discussion Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales.

Non-injection drug use and HIV disease progression in the era of combination antiretroviral therapy

Little is known about the effects of non-injection drug use (NIDU) on HIV antiretroviral treatment outcomes. We conducted a systematic literature search and identified nine publications from prospective cohort studies investigating the relationship between NIDU and clinical HIV disease progression. Hazard ratios from studies estimating the effect of drug use on time to AIDS-related mortality ranged from 0.89 to 3.61, and only two of these were statistically significant. Hazard ratios from studies assessing time to an AIDS-defining event ranged from 1.19 to 2.51, with 8 of the 14 estimates falling between 1.55 and 1.65 regardless of drug use definition and measurement of use or frequency. It is suggested that NIDU may have a moderate effect of increasing the risk of progression to AIDS, but its impact on AIDS-related mortality is uncertain. NIDU may affect HIV antiretroviral treatment outcomes primarily through interaction with antiretroviral therapy and, to a lesser extent, through immune modulation and deterioration of general health. The limitations about published studies are discussed, and future perspectives on research on this topic are provided.

Socio-demographic and AIDS-related factors associated with tuberculosis stigma in southern Thailand: a quantitative, cross-sectional study of stigma among patients with TB and healthy community members

BackgroundTuberculosis (TB) remains one of the most important infectious diseases worldwide. A comprehensive approach towards disease control that addresses social factors including stigma is now advocated. Patients with TB report fears of isolation and rejection that may lead to delays in seeking care and could affect treatment adherence. Qualitative studies have identified socio-demographic, TB knowledge, and clinical determinants of TB stigma, but only one prior study has quantified these associations using formally developed and validated stigma scales. The purpose of this study was to measure TB stigma and identify factors associated with TB stigma among patients and healthy community members.MethodsA cross-sectional study was performed in southern Thailand among two different groups of participants: 480 patients with TB and 300 healthy community members. Data were collected on socio-demographic characteristics, TB knowledge, and clinical factors. Scales measuring perceived TB stigma, experienced/felt TB stigma, and perceived AIDS stigma were administered to patients with TB. Community members responded to a community TB stigma and community AIDS stigma scale, which contained the same items as the perceived stigma scales given to patients. Stigma scores could range from zero to 30, 33, or 36 depending on the scale. Three separate multivariable linear regressions were performed among patients with TB (perceived and experience/felt stigma) and community members (community stigma) to determine which factors were associated with higher mean TB stigma scores.ResultsOnly low level of education, belief that TB increases the chance of getting AIDS, and AIDS stigma were associated with higher TB stigma scores in all three analyses. Co-infection with HIV was associated with higher TB stigma among patients. All differences in mean stigma scores between index and referent levels of each factor were less than two points, except for incorrectly believing that TB increases the chance of getting AIDS (mean difference of 2.16; 95% CI: 1.38, 2.94) and knowing someone who died from TB (mean difference of 2.59; 95% CI: 0.96, 4.22).ConclusionThese results suggest that approaches addressing the dual TB/HIV epidemic may be needed to combat TB stigma and that simply correcting misconceptions about TB may have limited effects.

The relationship between injection and noninjection drug use and HIV disease progression

BACKGROUND Injection drug use is associated with poor HIV outcomes even among persons receiving highly active antiretroviral therapy (HAART), but there are limited data on the relationship between noninjection drug use and HIV disease progression. METHODS We conducted an observational study of HIV-infected persons entering care between January 1, 1999, and December 31, 2004, with follow-up through December 31, 2005. RESULTS There were 1,712 persons in the study cohort: 262 with a history of injection drug use, 785 with a history of noninjection drug use, and 665 with no history of drug use; 56% were White, and 24% were females. Median follow-up was 2.1 years, 33% had HAART prior to first visit, 40% initiated first HAART during the study period, and 306 (17.9%) had an AIDS-defining event or died. Adjusting for gender, age, race, prior antiretroviral use, CD4 cell count, and HIV-1 RNA, patients with a history of injection drug use were more likely to advance to AIDS or death than nonusers (adjusted hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.43-2.70, p < .01). There was no statistically significant difference of disease progression between noninjection drug users and nonusers (HR = 1.19, 95% CI = 0.92-1.56, p = .19). An analysis among the subgroup who initiated their first HAART during the study period (n = 687) showed a similar pattern (injection drug users: HR = 1.83, 95% CI = 1.09-3.06, p = .02; noninjection drug users: HR = 1.21, 95% CI = 0.81-1.80, p = .35). Seventy-four patients had active injection drug use during the study period, 768 active noninjection drug use, and 870 no substance use. Analyses based on active drug use during the study period did not substantially differ from those based on history of drug use. CONCLUSIONS This study shows no relationship between noninjection drug use and HIV disease progression. This study is limited by using history of drug use and combining different types of drugs. Further studies ascertaining specific type and extent of noninjection drug use prospectively, and with longer follow-up, are needed.

Active cocaine use is associated with lack of HIV-1 virologic suppression independent of nonadherence to antiretroviral therapy: use of a rapid screening tool during routine clinic visits.

Abstract Clarifying the relationship between illicit drug use and HIV-1 virologic suppression requires characterization of both illicit drug use activity and adherence to antiretroviral therapy (ART). We developed a rapid clinical questionnaire to assess prior 7-day illicit drug use and ART adherence in a cross-sectional study among 1777 HIV-infected persons in care. Of these, 76% were male, 35% were African-American, and 8% reported injection drug use as their probable route of HIV-1 infection. Questionnaire-reported frequencies of cocaine and marijuana use within the previous 7 days were 3.3% and 12.1%, respectively. Over three quarters (77.8%) of participants were on ART, of whom 69.7% had HIV-1 virologic suppression (HIV-1 RNA<48 copies/mL). Univariate analyses revealed that compared to no use, cocaine and marijuana use were both associated with missed ART doses (P<0.01). Multivariable logistic regression analysis adjusting for nonadherence demonstrated that cocaine use was independently associated with failing to achieve virologic suppression (adjusted odds ratio (aOR): 0.46; 95% confidence interval (95% CI): 0.22–0.98) but marijuana use was not (aOR: 1.08; 95% CI: 0.72–1.62). This result strengthens the evidence of a direct effect of cocaine on virologic control, independent of nonadherence to ART.

Subjective Ratings of Fatigue and Vigor in Adults With Hearing Loss Are Driven by Perceived Hearing Difficulties Not Degree of Hearing Loss.

Objectives: Anecdotal reports and qualitative research suggests that fatigue is a common, but often overlooked, accompaniment of hearing loss which negatively affects quality of life. However, systematic research examining the relationship between hearing loss and fatigue is limited. In this study, the authors examined relationships between hearing loss and various domains of fatigue and vigor using standardized and validated measures. Relationships between subjective ratings of multidimensional fatigue and vigor and the social and emotional consequences of hearing loss were also explored. Design: Subjective ratings of fatigue and vigor were assessed using the profile of mood states and the multidimensional fatigue symptom inventory-short form. To assess the social and emotional impact of hearing loss participants also completed, depending on their age, the hearing handicap inventory for the elderly or adults. Responses were obtained from 149 adults (mean age = 66.1 years, range 22 to 94 years), who had scheduled a hearing test and/or a hearing aid selection at the Vanderbilt Bill Wilkerson Center Audiology clinic. These data were used to explore relationships between audiometric and demographic (i.e., age and gender) factors, fatigue, and hearing handicap scores. Results: Compared with normative data, adults seeking help for their hearing difficulties in this study reported significantly less vigor and more fatigue. Reports of severe vigor/fatigue problems (ratings exceeding normative means by ±1.5 standard deviations) were also increased in the study sample compared with that of normative data. Regression analyses, with adjustments for age and gender, revealed that the subjective percepts of fatigue, regardless of domain, and vigor were not strongly associated with degree of hearing loss. However, similar analyses controlling for age, gender, and degree of hearing loss showed a strong association between measures of fatigue and vigor (multidimensional fatigue symptom inventory-short form scores) and the social and emotional consequences of hearing loss (hearing handicap inventory for the elderly/adults scores). Conclusions: Adults seeking help for hearing difficulties are more likely to experience severe fatigue and vigor problems; surprisingly, this increased risk appears unrelated to degree of hearing loss. However, the negative psychosocial consequences of hearing loss are strongly associated with subjective ratings of fatigue, across all domains, and vigor. Additional research is needed to define the pathogenesis of hearing loss-related fatigue and to identify factors that may modulate and mediate (e.g., hearing aid or cochlear implant use) its impact.

Factors associated with declining under-five mortality rates from 2000 to 2013: an ecological analysis of 46 African countries

Objective Inadequate overall progress has been made towards the 4th Millennium Development Goal of reducing under-five mortality rates by two-thirds between 1990 and 2015. Progress has been variable across African countries. We examined health, economic and social factors potentially associated with reductions in under-five mortality (U5M) from 2000 to 2013. Setting Ecological analysis using publicly available data from the 46 nations within the WHO African Region. Outcome measures We assessed the annual rate of change (ARC) of 70 different factors and their association with the annual rate of reduction (ARR) of U5M rates using robust linear regression models. Results Most factors improved over the study period for most countries, with the largest increases seen for economic or technological development and external financing factors. The median (IQR) U5M ARR was 3.6% (2.8 to 5.1%). Only 4 of 70 factors demonstrated a strong and significant association with U5M ARRs, adjusting for potential confounders. Higher ARRs were associated with more rapidly increasing coverage of seeking treatment for acute respiratory infection (β=0.22 (ie, a 1% increase in the ARC was associated with a 0.22% increase in ARR); 90% CI 0.09 to 0.35; p=0.01), increasing health expenditure relative to gross domestic product (β=0.26; 95% CI 0.11 to 0.41; p=0.02), increasing fertility rate (β=0.54; 95% CI 0.07 to 1.02; p=0.07) and decreasing maternal mortality ratio (β=−0.47; 95% CI −0.69 to −0.24; p<0.01). The majority of factors showed no association or raised validity concerns due to missing data from a large number of countries. Conclusions Improvements in sociodemographic, maternal health and governance and financing factors were more likely associated with U5M ARR. These underscore the essential role of contextual factors facilitating child health interventions and services. Surveillance of these factors could help monitor which countries need additional support in reducing U5M.

Study of tuberculosis and AIDS stigma as barriers to tuberculosis treatment adherence using validated stigma scales

BACKGROUND Adherence to tuberculosis (TB) treatment is important for TB control. The effect of stigma on adherence has not been well quantified. OBJECTIVE To identify the effects of TB and acquired immune-deficiency syndrome (AIDS) stigma on missed doses during TB treatment. DESIGN Validated TB and AIDS stigma scales assessing perceived and experienced/felt stigma were administered in a prospective cohort of 459 TB patients at TB treatment initiation and after 2 months. Repeated measures and multivariable models estimated the effects of stigma on the rate of missed doses. RESULTS Fifty-six per cent of patients missed no doses, and associations between stigma and missed doses were minimal. Heterogeneity of effects was observed, how- ever, with higher experienced and felt TB stigma increasing missed doses among women (adjusted RR 1.22, 95%CI 1.10-1.34) and human immunodeficiency virus (HIV) co-infected patients (aRR 1.39, 95%CI 1.13-1.72). Experienced and felt AIDS stigma also increased missed doses among HIV co-infected patients (aRR 1.43, 95%CI 1.31-1.56). CONCLUSION Stigma has a minimal effect in this population with good adherence. Among women and HIV co-infected patients, however, experienced and felt stigma, and not perceived stigma, increased the rate of missed doses. Further research is needed to determine if stigma or coping interventions among these subgroups would improve adherence.